Companies are centralizing biomarker research to help reduce spending.

March 8, 2005 | As the elusive and expensive search for validated molecular biomarkers continues apace, medical and research proponents remain optimistic that the utilization of these entities will lead to better, safer, and cheaper therapeutics. With current estimates for successful drug development hovering in the $800-million to $1.5-billion range, the implications of finding relevant markers to predict toxicity, efficacy, and treatment outcomes are profound. Identifying such markers facilitates earlier go/no-go decisions in drug development.

So, what does the future hold for biomarker research and applications? In a recent survey of opinion leaders, Life Science Insights has determined that the hunt for specific, sensitive indicators has fueled investments in new technologies and research. Indeed, investments have increased more than 200 percent in the past several years and will double in the next few years, driven by industry trends, technology innovation, implementation of past investments, and recognized need. An additional driver in the post-Vioxx era will be regulatory requirements.

Clearly, spending in this area is driven by multiple factors and identification and validation of specific biomarkers, or an emerging new technology will lead to additional investment. Closely tied to this is an increased need for investment in data integration and data-mining tools to organize the vast quantities of captured information.

With the potential of "early kills" before costly clinical trial phases, companies can save in both money and resource prioritization. To help accomplish this, companies are centralizing biomarker research, to the point where it is becoming a standalone function. Although few companies currently have dedicated research solely for biomarker discovery, many incorporate biomarkers as compounds move through the development process, especially markers for mechanism, toxicity, and efficacy. The goal of having relevant markers that can be moved from pre-clinical testing to clinical trials, as well as having fewer, reliable markers to track as a drug goes into the clinical setting are key to reduced spending.

The Critical Path Initiative, published by the FDA in April 2004, outlines the agency's goals in the coming years, in cooperation with drug companies, to safely expedite drugs through clinical trials and increase the predictability of drug success. With half of all drugs entering Phase III failing to emerge as new therapeutics, the availability of biomarkers early in clinical trials could benefit attrition rates. Most companies surveyed have begun to voluntarily submit unvalidated biomarkers to the FDA as part of their new drug filings.

In a recent Webcast update (see www.connectlive.com/ events/fdacriticalpath), the FDA discussed the potential of an enrichment clinical trial design, where use of prospectively identified biomarkers could reduce the number of patients enrolled while decreasing the number of adverse events for patients. By understanding who is likely to respond to which drug, biomarkers can change the risk/benefit ratio for patients in clinical trials by enriching the population of patients who will benefit, as well as reducing the likelihood of adverse events. With smaller enrollments, faster trials, and higher success rates, companies can expect a greater market share for successful drugs, and physicians will have clearer guidance on better drug choices for their patients.To date, successful inroads have been made in oncology and AIDS, with recent reports showing promise for biomarker discovery in autoimmune disorders such as rheumatoid arthritis (RA). For example, Millennium Pharmaceuticals recently announced the discovery, utilizing mass spectrometry, of a panel of protein biomarkers that are elevated in patients with erosive RA. Early detection of these biomarkers could ultimately alter physician care management with earlier, more aggressive treatment regimens. In January, ChondroGene and researchers from UC-San Diego and Harvard published findings that blood-derived RNA from patients with schizophrenia and bipolar disorder expressed unique genomic signatures. This discovery could ultimately reveal disease biomarkers as well as the potential for better differentiating diagnoses for these two diseases.